HIV-induced IL-6/IL-10 dysregulation of CD4 cells is associated with defective B cell help and autoantibody formation against CD4 cells.
To analyse CD4 cell cytokine secretion and helper/suppressor function at a clonal level we established 446 CD4+ T cell clones (TCC) in four healthy controls, three HIV- haemophilia patients, four CDC II,III and four CDC IV patients. Spontaneous TCC secretion of Th1 cytokines (IL-2, interferon-gamma (IFN-gamma)) and Th2 cytokines (IL-4, IL-6, IL-10) was determined by ELISA. TCC helper and suppressor functions were tested in a pokeweed mitogen (PWM)-stimulated allogeneic co-culture system using a reverse haemolytic plaque assay for assessment of B cell responses. There was a significant association of TCC surface marker expression (Leu-8, CD45RA) with TCC IL-6 secretion in healthy controls (P < 0.01), HIV- patients (P < or = 0.001) and CDC II,III patients (P < or = 0.01) but not in CDC IV patients. Likewise, TCC expression of Leu-8 and CD45RA was significantly associated with TCC suppressor function in healthy controls (P < or = 0.0005) but not in HIV-infected patients. A reduced TCC helper frequency (< or = 10% of TCC) and an enhanced TCC suppressor frequency (> 80% of TCC) were detected only in those HIV-infected patients who showed an excessively increased TCC IL-6 secretion (> 70% of TCC) together with a significantly diminished TCC IL-10 secretion (< or = 10% of TCC). CD4 cell autoantibodies also were found only in patients with this type of cytokine dysregulation. These data indicate that CD4 cell surface markers lose their functional relevance in HIV-infected patients. HIV-induced IL-6/IL-10 dysregulation of CD4+ T cells, i.e. the up-regulation of spontaneous IL-6 and down-regulation of spontaneous IL-10 secretion, appears to be involved in inducing CD4 helper defects and may promote autoantibody formation against CD4 cells.
Weimer
R
R
Institute of Immunology, University of Heidelberg, Germany.
Zipperle
S
S
Daniel
V
V
Zimmermann
R
R
Schimpf
K
K
Opelz
G
G
D001323:Autoantibodies / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D015704:CD4 Antigens / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D015550:Cell Degranulation / Q000276:immunology; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D016753:Interleukin-10 / Q000276:immunology* / Q000378:metabolism; D015850:Interleukin-6 / Q000276:immunology* / Q000378:metabolism; D008211:Lymphocyte Cooperation
D001323:Autoantibodies; D015704:CD4 Antigens; D015850:Interleukin-6; D016753:Interleukin-10